The malaria parasite exports hundreds of proteins to the red blood cell in order to commandeer the host cell for its own nefarious purposes. This proposal aims to study a protease called plasmepsin V. It has recently been discovered that plasmepsin V recognizes and cleaves a sequence on the proteins that the parasite has designated for export. This is crucial for proteins to get out into the host cell. The proposal addresses the questions: What is special about plasmepsin V compared with mammalian counterparts? What is the specificity of this enzyme for its substrate? How does plasmepsin V interact with other cellular components to ensure that proteins to be exported get to their destination? The proposed experiments will involve enzymology, site-directed mutagenesis and protein-protein interaction studies. The goal is to understand plasmepsin V function to inform antimalarial drug development efforts. PUBLIC HEALTH RELEVANCE: Malaria afflicts hundreds of millions of people worldwide and over a thousand a year in this country, mostly those that have recently been abroad. Because of drug resistance there is a desperate need for new antimalarial treatments. The proposed research will study an important new target for drug development.